Abstract
The odds risk of vertical transmission of human immunodeficiency virus(HIV) to preterm infants is almost four times that of term infants and may relate to maternal and neonatal factors. We characterized the competence of early nonspecific cellular immunity, namely natural killer cytotoxicity (NKC) and antibody-dependent cellular cytotoxicity (ADCC), of peripheral blood mononuclear cells (PBMC) from preterm (n = 20) and term neonates(n = 28) versus adult controls against a T cell line infected with the human T cell lymphotrophic virus-IIIB using a chromium-51 release assay. PBMC from term neonates exhibited levels of NKC activity equal to adults against HIV-infected targets, yet the NKC capacity of preterm neonatal PBMC was significantly diminished. The ADCC activity of both term and preterm neonatal PBMC against HIV-infected targets was significantly less than that of adult PBMC. Overnight stimulation of a subset of samples with IL-12 augmented the NKC activity of both infant groups and adults, whereas the ADCC activity remained unchanged. These findings demonstrate that term neonates are deficient in ADCC against HIV-infected targets, whereas preterm infants are deficient in both NKC and ADCC, which may relate, in part, to the increased risk of transmission of HIV with preterm delivery. In addition, IL-12 has the potential to augment both term and preterm neonatal antiviral defense.
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Abbreviations
- HIV:
-
human immunodeficiency virus
- NK:
-
natural killer
- NKC:
-
natural killer cytotoxicity
- ADCC:
-
antibody-dependent cellular cytotoxicity
- PBMC:
-
peripheral blood mononuclear cells
- E:T:
-
effector-to-target
References
Newell ML, Dunn D, Peckham CS, Ades AE, Pardi G, Semprini AE 1992 Risk factors for mother-to-child transmission of HIV-1. European Collaborative Study [see comments]. Lancet 339: 1007–1012
Abrams EJ, Matheson PB, Thomas PA, Thea DM, Krasinski K, Lambert G, Shaffer N, Bamji M, Hutson D, Grimm K, Kaul A, Bateman D, Rogers M 1995 Neonatal predictors of infection status and early death among 332 infants at risk of HIV-1 infection monitored prospectively from birth. New York City Perinatal HIV Transmission Collaborative Study Group. Pediatrics 96: 451–458
Uksila J, Lassila O, Hirvonen T 1982 Natural killer cell function of human neonatal lymphocytes. Clin Exp Immunol 48: 649–654
Ueno Y, Miyawaki T, Seki H, Matsuda A, Taga K, Sato H, Taniguchi N 1985 Differential effects of recombinant human interferon-gamma and interleukin 2 on natural killer cell activity of peripheral blood in early human development. J Immunol 135: 180–184
Sancho L, de la Hera A, Casas J, Vaquer S, Martinez C, Alvarez MM 1991 Two different maturational stages of natural killer lymphocytes in human newborn infants. J Pediatr 119: 446–454
Nair MP, Schwartz SA, Menon M 1985 Association of decreased natural and antibody-dependent cellular cytotoxicity and production of natural killer cytotoxic factor and interferon in neonates. Cell Immunol 94: 159–171
McDonald T, Sneed J, Valenski WR, Dockter M, Cooke R, Herrod HG 1992 Natural killer cell activity in very low birth weight infants. Pediatr Res 31: 376–380
Yabuhara A, Kawai H, Komiyama A 1990 Development of natural killer cytotoxicity during childhood: marked increases in number of natural killer cells with adequate cytotoxic abilities during infancy to early childhood. Pediatr Res 28: 316–322
Uksila J, Lassila O, Hirvonen T, Toivanen P 1983 Development of natural killer cell function in the human fetus. J Immunol 130: 153–156
Baley JE, Schacter BZ 1985 Mechanisms of diminished natural killer cell activity in pregnant women and neonates. J Immunol 134: 3042–3048
Kohl S, Loo LS, Gonik B 1984 Analysis in human neonates of defective antibody-dependent cellular cytotoxicity and natural killer cytotoxicity to herpes simplex virus-infected cells. J Infect Dis 150: 14–19
Leibson PJ, Hunter LM, Douvas GS, Hayward AR 1986 Impaired neonatal natural killer-cell activity to herpes simplex virus: decreased inhibition of viral replication and altered response to lymphokines. J Clin Immunol 6: 216–224
Kunitomi T, Takigawa H, Sugita M, Nuono S, Suemune M, Inue M, Kodani N, Oda M, Ikeda M 1990 Antibody-dependent cellular cytotoxicity and natural killer activity against HTLV-1 infected cells. Acta Paediatr Jpn 32: 16–19
Jenkins M, Mills J, Kohl S 1993 Natural killer cytotoxicity and antibody-dependent cellular cytotoxicity of human immunodeficiency virus-infected cells by leukocytes from human neonates and adults. Pediatr Res 33: 469–474
Erkeller YF, Deneys V, Yuksel B, Hannet I, Hulstaert F, Hamilton C, Mackinnon H, Stokes LT, Munhyeshuli V, Vanlangendonck F, De Bruyere M, Bach BA, Lydyard PM 1992 Age-related changes in human blood lymphocyte subpopulations. J Pediatr 120: 216–222
Kohl S 1983 Defective infant antiviral cytotoxicity to herpes simplex virus-infected cells. J Pediatr 102: 885–888
Potter CG, Potter AC 1988 A rapid and ultra-simplified method for separating lymphocytes from blood. J Immunol Methods 112: 143–144
Blumberg RS, Paradis T, Hartshorn KL, Vogt M, Ho DD, Hirsch MS, Leban J, Sato VL, Schooley RT 1987 Antibody-dependent cell-mediated cytotoxicity against cells infected with the human immunodeficiency virus. J Infect Dis 156: 878–884
Lau AS, Sigaroudinia M, Yeung M, Kohl S 1994 Interleukin-12 (IL-12) induces interferon-gamma (IFN-gamma) expression and natural killer (NK) cell activity in cord blood mononuclear cells (MC). Pediatr Res 35: 300A
Rappocciolo G, Toso JF, Torpey DJ, Gupta P, Rinaldo C 1989 Association of alpha interferon production with natural killer cell lysis of U937 cells infected with human immunodeficiency virus. J Clin Microbiol 27: 41–48
Goicoa MA, Sen L, Iannitelli PS, Diez RA, Estevez ME 1995 Natural killer suppressor factors in sera from HIV-infected subjects. Scand J Immunol 41: 523–528
Cauda R, Tumbarello M, Ortona L, Kanda P, Kennedy RC, Chanh TC 1988 Inhibition of normal human natural killer cell activity by human immunodeficiency virus synthetic transmembrane peptides. Cell Immunol 115: 57–65
Harris DT, Cianciolo GJ, Snyderman R, Argov S, Koren HS 1987 Inhibition of human natural killer cell activity by a synthetic peptide homologous to a conserved region in the retroviral protein, p15E. J Immunol 138: 889–894
Sirianni MC, Tagliaferri F, Aiuti F 1990 Pathogenesis of the natural killer cell deficiency in AIDS. Immunol Today 11: 81–82
Vivier E, Morin P, O'Brien C, Druker B, Schlossman SR, Anderson P 1991 Tryosine phosphorylation of the Fc gamma RIII (CD16): zeta complex in human natural killer cells. J Immunol 146: 206–210
Bonnema JD, Karnitz LM, Schoon RA, Abraham RT, Leibson PJ 1994 Fc receptor stimulation of phosphatidylinositol 3-kinase in natural killer cells is associated with protein kinase C-independent granule release and cell-mediated cytotoxicity. J Exp Med 180: 1427–1435
Payne NR, Frestedt J, Hunkeler N, Gehrz R 1993 Cell-surface expression of immunoglobulin G receptors on the polymorphonuclear leukocytes and monocytes of extremely premature infants. Pediatr Res 33: 452–457
Gatti G, Cavallo R, Sartori ML, del PD, Masera R, Salvadori A, Carignola R, Angeli A 1987 Inhibition by cortisol of human natural killer (NK) cell activity. J Steroid Biochem 26: 49–58
Holbrook NJ, Cox WI, Horner HC 1983 Direct suppression of natural killer activity in human peripheral blood leukocyte cultures by glucocorticoids and its modulation by interferon. Cancer Res 43: 4019–4025
Murthy KK, Moya FR 1994 Effect of betamethasone on maternal, fetal and neonatal rat cellular immunity. Early Hum Dev 36: 1–11
Lazzarin A, Luerti M, Capsoni F, Galli M, Uberti-Foppa C, Zavattini G, Corbella E 1986 A study of cellular immunity in newborns after prevention of Respiratory Distress Syndrome (RDS). Int J Tissue React 8: 157–165
Wilson CB, Lewis DB 1990 Basis and implications of selectively diminished cytokine production in neonatal susceptibility to infection. Rev Infect Dis 12( suppl 4): S410–S420
Wu CY, Demeure C, Kiniwa M, Gately M, Delespesse G 1993 IL-12 induces the production of IFN-γ by neonatal human CD4 T cells. J Immunol 151: 1938–1949
Scott ME, Kubin M, Trinchieri G, Kohl S 1995 Neonatal competence for Interleukin-12 (IL12) production. J Pediatr 37: 285A
Suen Y, Lee SM, Chang L, Knoppel E, van de Ven C, Cairo MS 1995 Decreased IL-12 and IFN-γ production from neonatal mononuclear cells (MNC): implication in the immaturity of neonatal cellular immunity. J Pediatr 37: 286A
Chehimi J, Starr SE, Frank I, Rengaraju M, Jackson SJ, Llanes C, Kobayashi M, Perussia B, Young D, Nickbarg E, Wolf SF, Trinchieri G 1992 Natural killer (NK) cell stimulatory factor increases the cytotoxicity activity of NK cells from both healthy donors and human immunodeficiency virus-infected patients. J Exp Med 175: 789–796
Acknowledgements
The authors thank the nurses at the Pediatric Clinical Research Center for their assistance with this project.
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Supported in part by National Institutes of Health Grants AI32384 and MO1RR01271, Pediatric Clinical Research Center, and National Institute of Child Health and Human Development Grant HD07162.
Presented in part at the Annual Meeting of the Society for Pediatric Research, May 1996, Washington, D.C.
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Merrill, J., Sigaroudinia, M. & Kohl, S. Characterization of Natural Killer and Antibody-Dependent Cellular Cytotoxicity of Preterm Infants against Human Immunodeficiency Virus-Infected Cells. Pediatr Res 40, 498–503 (1996). https://doi.org/10.1203/00006450-199609000-00021
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DOI: https://doi.org/10.1203/00006450-199609000-00021
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